Integrated tissue processing and embedding systems, and methods thereof

ABSTRACT

Apparatus and methods for integrating tissue processors and embedding systems. An apparatus, of one aspect, includes a robot. The robot has a work envelope that encompasses a location having a tissue holder and an input of an embedding system. The tissue holder has at least one processed tissue. The robot is configured to transfer the tissue holder from the location to the input of the embedding system. A method, of one aspect, may include moving a robot to a location having a tissue holder. The tissue holder may have at least one processed tissue. The robot may engage with the tissue holder at the location. The robot may move the tissue holder from the location to an input to an embedding system. The robot may disengage from the tissue holder at the input to the embedding system. Other methods, apparatus, and systems are also disclosed.

BACKGROUND

1. Field

Integrated tissue processing and embedding systems, and methods.

2. Background Information

Histology is a science or discipline associated with the processing oftissue for examination or analysis. The examination or analysis may beof the cellular morphology, chemical composition, tissue structure orcomposition, or other tissue characteristics. Histology is used inresearch, diagnostic, and other applications.

FIG. 1 is a block flow diagram of an embodiment of histological method100. This is just one representative histological method. Variousmodifications of this histological method exist, such as by adding,removing, and/or rearranging operations.

At block 101, grossing and fixation may be performed on tissue. Thetissue may represent tissue samples or specimens taken during biopsies,autopsies, surgeries, or other tissue extractions. The tissue may alsorepresent a pellet of tissue. Grossing the tissue may potentiallyinclude examining the tissue, describing the tissue, and trimming thetissue to an appropriate size and/or shape. Fixing or fixating thetissue may include placing the grossed tissue in a fixative solution,which may help to preserve the tissue and/or prevent decomposition.

After grossing and fixation, tissue processing may be performed on thetissue, at block 102. During tissue processing, the tissue may be driedor dehydrated by removing most or almost all of the water from thetissue. Commonly, such drying may be achieved by exposing the tissue toone or more dehydrating agents. After drying the tissue, clearing of thedehydrating agents may optionally be performed, and then wax (e.g.,paraffin), wax with added plasticizers, or another embedding agent maybe introduced or infiltrated into the dried tissue. In some cases, avacuum may be applied to assist with infiltration of the wax or otherembedding agent into the tissue.

As will be explained further below, it is common in histology to cut thetissue into a thin section, for example with a microtome. Cutting atissue that has not undergone tissue processing may tend to bechallenging. Without tissue processing, the tissue may be soft andfilled with water. Force exerted on the tissue by a blade that is usedto cut the tissue into the thin sections may tend to compress the tissueand force some of the water out of the tissue. The tissue may not fullydecompress after removal of the blade. This may tend to alter thestructure of the tissue, which in some cases may tend to hinderexamination or analysis. However, removing the water from the tissue,and infiltrating wax or another embedding agent into the tissue (e.g.,infiltrating into interstices of the tissue), may help to allow thetissue to be cut with less compression and/or alteration of the tissuestructure.

After tissue processing, embedding may be performed on the tissue, atblock 103. During embedding, the tissue that has been dried andinfiltrated with wax or another embedding agent during tissue processingmay be embedded in a block or other mass of wax, various polymers, oranother embedding medium. Representatively, the dried andwax-infiltrated tissue may be placed in a mold, melted wax may bedispensed over the tissue until the mold has been filled with the wax,and then the wax may be cooled and hardened. Embedding the tissue in theblock of wax may help to provide additional support during cutting orsectioning of the tissue.

After embedding, the tissue embedded in the block of wax may besectioned into thin tissue sections, at block 104. During sectioning amicrotome or other bladed instrument may be used to cut the tissueembedded in the block of wax into the thin sections. By way of example,the thickness of the tissue sections may range from about one to tenmicrons. The sections, or a ribbon of multiple sequentially cutsections, may be floated on warm water, or otherwise softened andflattened, and then placed on microscope slides and allowed to dry.

After sectioning, the wax is removed and the thin tissue sections may bestained, at block 105. During staining, the tissue sections may beexposed to various stains. The stains may combine with the tissuesections to provide contrast between tissue components, structures,molecules, or some combination thereof, depending upon the particularstains. Some stains combine non-specifically chemically with the tissue,whereas other stains combine specifically with certain bacteria types,enzymes, molecules, portions of molecules, etc.

After staining, coverslipping may be performed, at block 106. Duringcoverslipping, a protective transparent cover may be applied over thestained tissue section. Coverslipping may aid in microscopic evaluationand/or may help to protect the tissue section from exposure to air andsubsequent handling.

Currently, tissue processing is often performed automatically by aninstrument known as an automated tissue processor. Likewise, embeddingis often performed automatically by an instrument known as an automatedembedding system. However, the automated tissue processor and theautomated embedding system are currently separate, unconnectedinstruments.

Accordingly, after tissue processing has been performed, the tissue thathas been dried and infiltrated with wax or another embedding agent needsto be manually removed from the automated tissue processor, moved to,and introduced into the automated embedding system before embedding maybegin. Despite the automation within each of the separate instruments,manual unloading, transfer, and loading of tissue from the automatedtissue processor to the automated embedding system is necessary.

Performing such operations manually tends to unnecessarily occupy thetime of laboratory personnel, often at short intervals. This may tend toprevent or compete with the personnel performing other possibly morevaluable services. In addition, due to other tasks, the personnel maynot always transfer tissue from one instrument to the other as soon aspossible, which may potentially lead to instrument downtime, and reducedproductivity or throughput.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The invention may best be understood by referring to the followingdescription and accompanying drawings that are used to illustrateembodiments. In the drawings:

FIG. 1 is a block flow diagram of an embodiment of a histologicalmethod.

FIG. 2 is a block diagram of a first embodiment of an integrated tissueprocessing and embedding system.

FIG. 3 is a representative embodiment of a tissue cassette.

FIG. 4 is a representative embodiment of a magazine.

FIG. 5 is a block flow diagram of an embodiment of a method ofrobotically transferring a magazine from an output of a tissue processorto an input of an embedding system with a robot.

FIG. 6 is a block diagram of a second embodiment of an integrated tissueprocessing and embedding system.

FIG. 7 is a block flow diagram of an embodiment of a method ofrobotically transferring a magazine from an output of a tissue processorindirectly to an input of an embedding system via an intermediatestorage location.

FIG. 8 is a block diagram of another embodiment of an integrated tissueprocessing and embedding system.

FIG. 9A is a block flow diagram of an embodiment of a method ofrobotically transferring an empty magazine from an empty magazine outputof an embedding system to an integration unit.

FIG. 9B illustrates an embodiment of a cleaning mechanism.

FIG. 10A is a diagram of another embodiment of an integrated tissueprocessing and embedding system.

FIG. 10B is an expanded front view of the robot of FIG. 10A.

FIG. 10C is an expanded side, partial perspective, view of an embodimentof an end effector.

FIG. 11 is a block diagram of a fifth embodiment of an integrated tissueprocessing and embedding system, along with an embedding system.

FIG. 12 is a block diagram of a sixth embodiment of an integrated tissueprocessing and embedding system, along with a tissue processor.

FIG. 13 is a diagram of a seventh embodiment of an even more highlyintegrated tissue processing and embedding system.

DETAILED DESCRIPTION

FIG. 2 is a block diagram of a first embodiment of integrated tissueprocessing and embedding system 210. For convenience, the integratedtissue processing and embedding system may be referred to simply as anintegrated system.

The integrated system includes tissue processor 212, embedding system230, and tissue processor/embedding system integration unit 224. Thetissue processor and the embedding system may perform their individualfunctions according to known instruments. As such, a detailedunderstanding of the inner mechanisms or workings of the tissueprocessor and the embedding system are not necessary. Accordingly, onlya brief description will be provided.

Initially, a magazine having multiple cassettes, for example, may beinput into the tissue processor through an input (not shown). Each ofthe cassettes may have a tissue, which has potentially been grossedand/or fixated.

FIG. 3 is a representative embodiment of cassette 340 which is suitable.In this embodiment, cassette 340 is a clam shaped cassette having top341 and bottom 342 joined by hinge or other joint 344. The cassette maybe opened to receive a tissue within compartment 343, and then thecassette may be closed around the tissue. As shown, the cassette mayhave an open structure defining a number of slits, holes, perforations,or other openings. These openings may allow access to the tissue byliquids, such as dehydrants, liquid wax, and the like. In one or moreembodiments, the cassette may include a TISSUE-TEK® PARAFORM® brandsectionable cassette system having a unique PARAFORM® material, which iscommercially available from Sakura Finetek USA, Inc., of Torrance,Calif. The PARAFORM® material allows sectioning directly through thecassette. Alternatively, various other commercially available cassettesare also suitable.

FIG. 4 is a representative embodiment of magazine 222 which is suitable.Magazine 222 includes door or cover 445 and compartment 446. Magazine222 is held by hanger 447. In this embodiment, hanger 447 may supporttwo magazines, though only magazine 222 is shown. A plurality ofcassettes, such as, for example, about 20 cassettes, may be introducedinto magazine 222, into predefined slots, divisions, or other cassettelocations, with one cassette arranged vertically over another as viewed.Once the cassettes are loaded, door 445 may be closed, enclosing thecassettes in the magazine. As illustrated in FIG. 4, magazine 222 mayhave an open structure defining a generally large number of slits,holes, perforations, or other openings. An indication of compartment 446is indicated by an arrow extending through an opening to point to thecompartment. These openings may allow access to the cassettes byliquids, such as dehydrants, liquid wax, embedding agents, and the like.The magazine represents a convenient way to carry or handle multiplecassettes.

It is to be appreciated that the size, shape, design, appearance,materials, and manner of operation of cassettes and magazines may varywidely from one implementation to another. As such, the terms cassetteand magazine are to be interpreted broadly as tissue holder or carrierdevices, mechanisms, or structures. As used herein a cassette holds asingle sample of tissue, whereas a magazine holds multiple samples oftissue, often with each tissue being held by a different correspondingcassette.

Referring again to FIG. 2, tissue processor 212 includes tissueprocessing mechanism 214. The tissue processing mechanism includestissue drying mechanism 216 to dry or remove at least some of the fluid(e.g. water) from each of the tissues. Tissue drying mechanism 216 mayinclude one or more dehydrants. Tissue drying mechanism 216 may alsooptionally include a clearing agent to clear the dehydrants from thetissue. Tissue drying mechanism 216 may also include a cassette handlingmechanism to move the tissue around to the one or more dehydrants and/orclearants, and/or tubes or other flow conduits, and valves or other flowregulation devices, to move the one or more dehydrants and/or theclearants to the tissue.

Tissue processing mechanism 214 also includes infiltration mechanism 218to infiltrate wax (e.g., paraffin), or another embedding agent (e.g., apolymer), into the tissue after a fluid removal operation. Infiltrationmechanism 218 may include a source of liquid wax or another liquidembedding agent. In some cases, the infiltration mechanism mayoptionally include a vacuum to assist with the infiltration.

Magazine 222A having a plurality of cassettes, with each of thecassettes having a processed tissue, may be output from the tissueprocessor at output 220. Each processed tissue may represent a dried andinfiltrated tissue, from which at least some of the fluid (e.g. water)has been removed, and into which wax or another embedding agent has beeninfiltrated.

One particular example of a suitable tissue processor is the TISSUE-TEK®XPRESS® X120 brand rapid tissue processor, which is commerciallyavailable from Sakura Finetek USA, Inc., of Torrance, Calif. TheTISSUE-TEK® XPRESS® X120 brand rapid tissue processor has one loadingstation and two unloading stations. After a magazine having cassetteshas been loaded into the loading station, the TISSUE-TEK® XPRESS® X120brand rapid tissue processor may use microwave heating technology,dehydrants, an embedding agent, and vacuum assisted infiltrationtechniques to perform tissue processing. A finished magazine havingcassettes having dried and infiltrated tissue may be output through oneof the two unloading stations.

Referring again to FIG. 2, integrated system 210 also includes tissueprocessor/embedding system integration unit 224. For convenience, thetissue processor/embedding system integration unit may be referred toherein simply as an integration unit. The integration unit may automate,or at least partially automate, the transfer of magazines or othertissue holders between the tissue processor and the embedding system.

The integration unit includes robot 226. The term robot is to beinterpreted broadly as a conveyance, transfer device, electro-mechanicaltransfer device or mechanism, or automatically controlled,reprogrammable, multipurpose manipulator programmable in three, four, ormore axes. Robot 226 may take various forms or configurations,consistent with its intended purpose. For example, in variousembodiments, robot 226 may be a Gantry or Cartesian coordinate typerobot, a selective compliant assembly robot arm (SCARA) type robot, anarticulated arm type robot, or a combination thereof (e.g., a SCARA typerobot coupled in a Gantry type robot configuration), to name just a fewexamples.

In one or more embodiments, robot 226 may have a robotic arm or othermechanical limb. The arm or limb may include an interconnected set oftwo or more links and one or more powered joints. In one or moreembodiments, the arm or limb may allow rotation or movement in at leastfour axes. As is known, the flexibility or freedom of movement of thearm increases with increasing number of axes. The arm or limb maysupport and move an end-of-arm tooling or other end effector that isconnected at the end of the arm or limb.

The end effector may allow the robot to perform certain intendedfunctions, such as, for example, engaging with an item (e.g., a magazineor other tissue holder), holding and moving the item, and disengagingfrom the item. In one or more embodiments, the end effector may includea gripper. The gripper may serve as a “hand” to grasp, clasp, hook, orotherwise engage with, hold and move, and disengage from an item. As oneexample, the gripper may include two opposed jaws, claws, or fingerscoupled at a joint, or a pincer-like mechanism, which is able to openand close. Alternatively, a more sophisticated gripper having three ormore fingers may optionally be used. Another suitable end effector is ahook, which may be used to hook a ring, loop, opening in a handle, orother hookable structure on an item.

The integration unit and the robot are functionally or operativelycoupled or connected with the tissue processor and the embedding system.In one or more embodiments, the output of the tissue processor and theinput of the embedding system are within the “work envelope” of therobot.

In one or more embodiments, the integration unit and the robot may bephysically coupled or connected between the tissue processor and theembedding system. For example, the robot may comprise a Gantry orCartesian coordinate type robot having a track, rail, other horizontalmember, or other linear axis extending between the tissue processor andthe embedding system. A carriage including an arm or limb of the robotand the end effector may move along a linear axis between the tissueprocessor and the embedding system. Such a robot will be discussed infurther detail below in conjunction with FIGS. 10A-10B. In addition tothe linear axis, the integration unit may also optionally include aframe, chassis, housing, or the like to physically couple the tissueprocessor with the embedding system.

Alternatively, there may be no permanent physical coupling or connectionbetween the integration unit, the tissue processor, and the embeddingsystem. For example, the robot may include an articulated arm type robotbetween, in front of, behind, or otherwise proximate the tissueprocessor and the embedding system, without permanent physicalconnection. By proximate it is meant that the output of the tissueprocessor and the input of the embedding system are within the “workenvelope” of the robot.

The robot may be programmed with an application program, programroutine, or other set of instructions. The program or set ofinstructions may specify one or more operations the robot is toautonomously or at least semi-autonomously perform. Representatively,the program or set of instructions may specify the movements (e.g.,coordinates, distances, directions, etc.), end effector actions, timingor triggers, and like information associated with the operations.

Referring again to FIG. 2, in one or more embodiments, as shown by arrow228, robot 226 may transfer magazine 222A (or another tissue holder)from output 220 of tissue processor 212 to input 238 of embedding system230. Input 238 of embedding system 230 may receive magazine 222B. The“A” and “B” in 222A and 222B, respectively, are used merely to indicatethe same magazine in different locations. In a sense, the robot mayrepresent a pick and place robot to pick and place the magazine.

Robotically transferring magazines or other tissue holders between thetissue processor and the embedding system, as opposed to manuallytransferring the magazines, offers certain potential advantages. For onething, it may free personnel from the necessity of having to performingthese sometimes repetitive or tedious operations manually.Advantageously, this may allow the personnel to perform more value-addedoperations and/or other operations less amenable to automation. Foranother thing, the robot may be better suited for performing theseoperations faithfully and timely than the personnel, who may at times bedistracted with other tasks, or forget or be unable to perform theseoperations faithfully or timely. Advantageously, this may allow improvedproductivity or throughput by reducing instrument downtime waiting forsamples to be transferred manually.

Referring again to FIG. 2, the embedding system includes embeddingmechanism 232. The embedding mechanism may include cassette handlingmechanism 234 to handle cassettes. In one embodiment, the cassettehandling mechanism may include robotics internal to the embeddingsystem. The cassette handling mechanism may remove cassettes from themagazine, and provide them to dispensing mechanism 236. The dispensingmechanism may include a source of liquid wax (e.g. paraffin) or anotherembedding medium, and may dispense the embedding medium on the cassettesand cool the embedding medium in order to embed the tissue in a block orother mass of the embedding medium.

One particular example of a suitable embedding system is the TISSUE-TEK®AUTOTEC® brand automated embedding system, which is also commerciallyavailable from Sakura Finetek USA, Inc. The TISSUE-TEK® AUTOTEC® brandautomated embedding system has a loading station or input, and fouroutput doors. After a magazine having cassettes has been input, theTISSUE-TEK® AUTOTEC® brand automated embedding system has internalrobotics to handle the cassettes within the instrument. The TISSUE-TEK®AUTOTEC® brand automated embedding system places the cassettes in molds,dispenses paraffin or other embedding medium into the molds, and coolsthe embedding medium to form blocks or other masses in which the tissueis embedded. The cassettes having the tissue embedded in the blocks arethen moved to one of the four output doors.

FIG. 5 is a block flow diagram of an embodiment of method 550 ofrobotically transferring a magazine or magazines (or other tissueholder) from an output of a tissue processor to an input of an embeddingsystem with a robot. The magazines being transferred may have cassettes,and each of the cassettes may have a processed tissue, from which fluidhas been at least partially or substantially removed, and into which waxor another embedding agent has been infiltrated.

The movement of a robot may be controlled by a controller (e.g., aprogrammable logic unit or a computer) that is electrically orcommunicatively linked to a tissue processor and an embedding system. Inone or more embodiments, movement or operation of the robot may be basedon signals exchanged between the controller and/or the integration unitand the tissue processor and/or the embedding system. For example, inone embodiment, such a controller may receive a signal from the tissueprocessor indicating that a magazine or magazines are in the tissueprocessor and are ready for embedding. In response, the controller maysignal the robot to retrieve the magazine(s) from the tissue processorand transfer them to the embedding system.

At block 551, the robot may move to the output of the tissue processor.As used herein, moving the robot does not necessarily mean moving thewhole robot. In one aspect, a portion of the robot (e.g., a portionhaving an end effector) may move, while another portion of the robot mayremain stationary. Of course, the robot need not move if the robotalready happens to be at the output of the tissue processor.

In one or more embodiments, prior to, at about the same time as, orshortly after the robot moves to the output, the tissue processor mayautonomously open the output in order to provide the robot access to themagazine or a signal from the controller may result in the tissueprocessor opening the output. For example, the tissue processor mayslide open a drawer, or open a door, cover, or other closure mechanism.In one or more embodiments, a conventional tissue processor may bemodified to incorporate a small motor, actuator, other mechanism, orother means for opening the output. Alternatively, the robot may openthe output, such as, for example, by pressing a button, flipping aswitch, pulling on a drawer, opening a door, sliding open a cover,lifting a lid, or performing another action, such as, for example, anaction that an operator would normally perform manually. Advantageously,this may allow a conventional tissue processor to be used without theaforementioned modification. Other approaches are also contemplated, forexample, the controller may receive a signal indicating that a magazineis ready for transfer, and the robot may move to a position, in whichmovement to the position trips a switch or otherwise signals the outputto open.

At block 552, the robot may engage with the magazine at the output ofthe tissue processor. For example, a gripper or other end effector maypinch, clamp, clasp, grip, grasp, or otherwise engage with the magazine.In some tissue processors, such as the TISSUE-TEK® XPRESS® X120 brandrapid tissue processor, instead of a single magazine being provided atthe output, two or more magazines connected by a hanger or otherconnector may be provided at the output. The robot may potentiallyengage the hanger. As used herein, the robot engaging with the magazine,the robot engaging with the tissue holder, and like phrases, encompassthe robot engaging with a hanger, other connector, or other structureconnected to one or more magazines.

In one or more embodiments, when engaging the item, the robot mayutilize native features or structures on the magazine or other tissuecarrier to improve the engagement or holding on the item. For example,natural grooves, ridges, protrusions, handles, or the like may beutilized. As another option, in one or more embodiments, the magazine orother tissue carrier may be adapted or modified to include dedicatedfeatures or structures to improve the engagement or holding on the item.Examples of such features or structures include, but are not limited to,handles or other parts designed specifically to be engaged by the robot,loops, rings, or other hookable structures capable of being hooked by ahook, to name just a few examples.

At block 553, the robot may move the magazine from the output of thetissue processor to the input of the embedding system. As shown by arrow228 in FIG. 2, in one or more embodiments, the robot may move themagazine from the output of the tissue processor directly to the inputof the embedding system. Alternatively, as will be discussed furtherbelow, as shown by arrows 657 and 659 in FIG. 6, in one or moreembodiments, the robot may move the magazine from the output of thetissue processor indirectly to the input of the embedding system via anintermediate storage location (e.g., storage location 656).

After the robot has moved the magazine out of the output of the tissueprocessor, in one or more embodiments, the tissue processor mayautonomously close the output, or a controller may direct the tissueprocessor to close the output by sending an appropriate signal to thetissue processor. Alternatively, the robot may optionally close theoutput before moving away.

In one or more embodiments, prior to, at about the same time as, orshortly after the robot moves to the input of the embedding system, theembedding system may autonomously open the input, or be directed to openthe input by a controller. For example, the embedding system may slideopen a drawer, or open a door, cover, lid, or other closure mechanism.In one or more embodiments, an otherwise conventional embedding systemmay be modified to incorporate a small motor, actuator, other mechanism,or other means for opening the input. By way of example, the TISSUE-TEK®AUTOTEC® brand automated embedding system may be modified so that leadscrews may be rotated to move a drawer outward. Alternatively, the robotmay open the input, such as, for example, by pressing a button, flippinga switch, pulling on a drawer, sliding open a cover, lifting a lid, orperforming another action, such as an action that an operator wouldnormally perform manually. This may allow a conventional embeddingsystem to be used without modification.

Some embedding systems may have two or more drawers or other locationswhere tissue holders may be input. In one or more embodiments, theembedding system may provide a signal or communication to the robotindicating one of the locations where the tissue holder is to be input.The robot may then move the tissue holder to the indicated location.

At block 554, the robot may disengage from the magazine at the input tothe embedding system. For example, the magazine may be dropped orotherwise loaded into the input of the embedding system. Then, the inputto the embedding system may be closed, either autonomously by theembedding system, or by the robot. At this point, embedding may beperformed in a conventional manner.

FIG. 6 is a block diagram of a second embodiment of integrated tissueprocessing and embedding system 610, which for convenience may simply bereferred to as integrated system. The integrated system includes tissueprocessor 212 and embedding system 230. The tissue processor and theembedding system, and their components and functions, may optionally besimilar to, or the same as, those of FIG. 2. To avoid obscuring thedescription, these aspects will not be repeated.

The integrated system also includes tissue processor/embedding systemintegration unit 624, or simply the integration unit. In an embodimentwhere a controller is linked to a tissue processor and an embeddingsystem to control the transfer of a magazine(s) from the tissueprocessor to the embedding system, the controller may also beelectronically linked to the integration unit.

Integration unit 624 has robot 626. Robot 626, and its components andfunctions, may be similar to those of robot 226 of FIG. 2, with a fewnotable exceptions discussed below.

As shown, in one or more embodiments, the integration unit may includestorage location 656. The storage location may be used to storemagazines or other tissue holders. The storage location is locatedoutside of the tissue processor and the embedding system.Representatively, in various embodiments, the storage location mayinclude a drawer, chamber, compartment, cabinet, enclosure, cubbyhole,or the like. The robot may be capable of introducing the magazine intothe storage location, and removing the magazine from the storagelocation.

In one or more embodiments, as shown by arrow 657, robot 626 maytransfer magazine 222A from output 220 of tissue processor 212 tostorage location 656. Subsequently, in one or more embodiments, as shownby arrow 659, the robot may transfer magazine 222B from the storagelocation to input 238 of embedding system 230 as magazine 222C.

As shown, in one or more embodiments, the integration unit mayoptionally include heater 658 to heat the storage location and/or themagazine or at least the tissue located in the storage location. Theheater may be within the storage location or proximate the storagelocation. Examples of suitable heaters include, but are not limited to,heat lamps (e.g., light bulbs that give off heat), heating coils,heating elements, resistance heaters, hot plates, hot pads, pipes havinghot water or other heating fluid flowing through them, electric heaters,radiative heaters, space heaters, and the like. In one or moreembodiments, the heater may heat the storage location to a temperaturein a range of about 50° C. to about 80° C., or from about 55° C. toabout 75° C., or from about 58° C. to about 72° C. If desired, theintegration unit may optionally include a temperature control system(not shown) to control the heater to attempt to maintain or control atemperature within the storage location and/or a temperature proximatethe tissue.

As shown, in one or more embodiments, the integration unit mayoptionally include hanger storage location 660 to store a hanger orother connector that is used to connect two or more magazines. Aspreviously discussed, some tissue processors, such as, for example, theTISSUE-TEK® XPRESS® X120 brand rapid tissue processor, provide two ormore magazines connected by a hanger or other connector. The robot maybe capable of disconnecting or otherwise removing the hanger or otherconnector from the magazines, and introducing the hanger or otherconnector into the hanger storage location. Examples of suitable hangerstorage locations include, but are not limited to, a rack, a rod, aring, a hook, or another structure or device that a hanger may be hungon. Alternatively, the robot may instead move the hanger to anotherlocation, such as back to the tissue processor.

FIG. 7 is a block flow diagram of an embodiment of a method 753 ofrobotically transferring or moving a magazine (or other tissue holder)from an output of a tissue processor indirectly to an input of anembedding system through an intermediate storage location with a robot.

At block 761, the robot may move the magazine away from the tissueprocessor and to the storage location, such as, for example, storagelocation 656 of integration unit 624. In one or more embodiments, priorto, at about the same time as, or shortly after the robot moves tostorage location, the integration unit and/or the robot may potentiallyautonomously open the storage location. For example, the integrationunit may slide open a drawer, or open a door, cover, lid, or otherclosure mechanism. Alternatively, the robot may open the storagelocation, such as, for example, by pressing a button, flipping a switch,pulling on a drawer, sliding open a cover, lifting a lid, or the like.

At block 762, the robot may disengage from the magazine at the storagelocation. If the magazine is connected to a hanger or other connector,along with potentially one or more other magazines, then the robot maydecouple the hanger or other connector from the magazine(s). The robotmay move the hanger or connector to a hanger storage location, such as,for example, hanger storage location 660.

In one or more embodiments, after the robot disengages from the magazineand moves out of the storage location, the integration unit and/or therobot may potentially close the storage location. Note that it is notrequired that the storage location be capable of being opened andclosed.

At block 763, the magazine may be stored at the storage location. In oneor more embodiments, on average the magazine may be stored at thestorage location for at least a brief period of time ranging from aboutat least one minute to about an hour, often from about two minutes toabout twenty minutes. Occasionally, such as, for example, if theembedding system needs additional cassettes, the time may be shorter, oroccasionally, such as, for example, if the embedding system is down, hasplenty of cassettes, or the like, the storage period may be longer.

At block 764, the magazine, or at least the infiltrated tissue, mayoptionally be heated while at the storage location. For example, heater658 may heat the storage location, the magazine, the cassettes, and/orthe infiltrated tissue. In one or more embodiments, the infiltratedtissue may be exposed to a temperature operable to heat the wax or otherembedding agent in the tissue to a softening or melting point over aperiod ranging from about 2 to about 20 minutes, in some cases fromabout 5 to 15 minutes. Temperatures conventionally employed in the inputof the TISSUE-TEK® AUTOTEC® brand automated embedding system aresuitable. However, this particular heating is not required, since anyheating may offer an advantage.

Conventionally, some embedding systems, such as, for example, theTISSUE-TEK® AUTOTEC® brand automated embedding system, heat theinfiltrated tissue for a period of time in the input before beginningthe embedding process. The time taken to heat the infiltrated tissue inthe input tends to increase the processing time for embedding and/orlimit the throughput of the embedding system. One advantage of heatingthe infiltrated tissue in the storage location is a reduction of thetime needed to heat the tissue in the input of the embedding system.This can help to reduce the processing time for embedding and/or improvethe throughput of the embedding system. Furthermore, some embeddingsystems may potentially lack the ability to pre-heat the tissue beforethe actual embedding.

Referring to FIG. 7, dashed line 765 is used to indicate a second halfof method 753, in which the magazine is transferred or moved from thestorage location to the input of the embedding system. Differentcriteria are possible for determining when to begin the second half ofthe method.

In one or more embodiments, the second half of the method may begin whenthe embedding system is ready to receive and/or process the magazine ortissue. For example, the embedding system may be capable of signaling tothe integration unit that the embedding system is or will be ready toreceive and/or process the magazine or tissue. This may be done througha control system (e.g., a programmable logic unit, a computer system, orother controller) that queries the embedding system whether it is readyto accept magazines for embedding (e.g., a load dock is queried whetherit is empty and the embedding system is queried whether a new processcan begin). Alternatively, in one or more embodiments, the second halfof the method may begin when the magazine has been stored at the storagelocation for a predetermined or fixed period of time.

At block 766, the robot may move to the storage location. Of course, therobot need not move if the robot already happens to be at the storagelocation.

In one or more embodiments, prior to, at about the same time as, orshortly after the robot moves to the storage location, the integrationunit and/or the robot may autonomously open the storage location (e.g.,a controller may signal the integration unit to open the storagelocation).

At block 767, the robot may engage with the magazine at the storagelocation. At block 768, the robot may move the magazine away from thestorage location and to the input to the embedding system.

In one or more embodiments, prior to, at about the same time as, orshortly after the robot moves to the input of the embedding system, theembedding system may autonomously open the input of the embeddingsystem. Alternatively, the robot may open the input of the embeddingsystem.

At block 769, the robot may place the magazine in the embedding systemat the input and disengage from the magazine at the input to theembedding system. In one or more embodiments, after the robot disengagesfrom the magazine and moves from the input, the embedding system mayautonomously close the input of the embedding system (e.g., a controllermay signal the embedding system to close the input). Alternatively, therobot may close the input.

At this point, embedding may be performed in a conventional manner. Atsome point, the embedding system will have removed all of the cassettesfrom the magazine. Accordingly, an empty magazine may exist at theembedding system. In one or more embodiments, an integration unit and/ora robot may optionally be capable of removing empty magazines from theembedding system. Advantageously, this may avoid the need to manuallyremove the empty magazine.

FIG. 8 is a block diagram of another embodiment of integrated tissueprocessing and embedding system 810, which for convenience may simply bereferred to as an integrated system. The integrated system includestissue processor 212 and embedding system 230. The tissue processor andthe embedding system, and their components and functions, may optionallybe similar to, or the same as, those of FIG. 2 and/or FIG. 6. To avoidobscuring the description, these aspects will not be repeated.

The integrated system also includes tissue processor/embedding systemintegration unit 824, which may simply be referred to as an integrationunit. The integration unit has robot 826. Robot 826 and its componentsand functions may be similar those of robot 226 of FIG. 2 and/or robot626 of FIG. 6, with a few notable exceptions discussed below.

As shown, in one or more embodiments, the integration unit mayoptionally include cleaning mechanism 870 housed within the integrationunit as a subsystem to clean empty magazines. In one or moreembodiments, cleaning the empty magazines may include removing wax fromthe empty magazines. Examples of suitable cleaning mechanisms include,but are not limited to, hot water power washing (e.g., a flow of atleast slightly pressurized heated water, for example heated to atemperature in a range of about 70° C. to about 95° C., or from about77° C. to about 87° C., with or without soap (often without soap so thatthe water can more easily be recycled), directed at the emptymagazines), baths of dewaxing solvents or compositions, showers ofdewaxing solvents or compositions, a hot water bath, a hot water shower,a steam treatment, heating to above the melting point of wax, ascrubbing mechanism, or the like, or combinations thereof. By way ofexample, the cleaning mechanism may be provided in a drawer, chamber,compartment, cabinet, enclosure, vessel, or the like. The robot may becapable of introducing the empty magazines into the cleaning mechanism.

In one or more embodiments, as shown by arrow 871, robot 826 maytransfer empty magazine 222A from empty magazine output 839 of embeddingsystem 230 to cleaning mechanism 870 as empty magazine 222B.

As shown, in one or more embodiments, the integration unit mayoptionally include empty magazine storage 872 to store empty magazines,which may potentially have been cleaned by cleaning mechanism. Examplesof suitable empty magazine storage include, but are not limited tocompartments, enclosures, drawers, cabinets, cubbyholes, shelves,hangers, racks, hooks, sacks, and the like.

FIG. 9A is a block flow diagram of an embodiment of a method 976 ofrobotically transferring or moving an empty magazine from an emptymagazine output of an embedding system to an integration unit.

In one or more embodiments, the embedding system may signal orcommunicate to the integration unit, control logic for the robot, and/orthe robot that the empty magazine is available (e.g., the last cassettehas been removed from the magazine). In one or more embodiments, thesignal or communication may also indicate one of multiple drawers orother locations where the empty magazine is located. Alternatively, inone or more embodiments, the integration unit and/or the robot mayinclude software or other logic to calculate or estimate when the emptymagazine will be available (e.g., based on when the full magazine wasdelivered and historical or otherwise known embedding system processingrates).

At block 977, the robot may move to the empty magazine output of theembedding system. Just prior to, at about the same time as, or shortlyafter the robot moves to the empty magazine output, in one or moreembodiments, the embedding system may autonomously open the emptymagazine output. Alternatively, the robot may open the empty magazineoutput.

At block 978, the robot may engage the empty magazine at the emptymagazine output. At block 979, the robot may lift the empty magazine outof the output and move the empty magazine from the empty magazine outputto the integration unit.

After the empty magazine has been removed from the output, in one ormore embodiments, the embedding system may autonomously close the emptymagazine output. Alternatively, the robot may close the empty magazineoutput.

At block 980, the robot may disengage from the empty magazine at theintegration unit. In various embodiments, the robot may disengage fromthe empty magazine at a cleaning mechanism (e.g., cleaning mechanism870) of the integration unit or at an empty magazine storage (e.g.,empty magazine storage 872) of the integration unit.

At block 981, the empty magazine may optionally be cleaned at theintegration unit. In one or more embodiments, cleaning the magazine mayinclude removing wax from the empty magazine. Advantageously, this mayavoid the need for personnel to manually clean the empty magazines.

At block 982, the empty magazine, which has potentially been cleaned,may optionally be stored at the integration unit, such as at emptymagazine storage 872. The robot may be capable of moving the emptymagazines from the cleaning mechanism to the empty magazine storage.Alternatively, the empty magazine may optionally be stored elsewhere,such as, for example, at the tissue processor, the embedding system, orother locations within the working envelope of the robot (e.g., on atable or work surface proximate the robot).

FIGS. 7 and 9 show example methods. These methods have been described ina basic form, but operations may optionally be added to and/or removedfrom the methods. Furthermore, certain operations of the methods mayalso optionally be performed in different order. For example, the secondhalf of method 753 of FIG. 7 (shown below dashed line 765) mayoptionally be performed after at least part of method 976 of FIG. 9A hasbeen performed. The order of such operations may be readily changed bychanging the application program or set of instructions used to controlthe operations performed by the robot.

FIG. 9B illustrates an embodiment of a cleaning mechanism 970. In one ormore embodiments, the cleaning mechanism may be included in anintegration unit.

The cleaning mechanism includes a tank 911. Inside the tank is a mesh orother openwork basket 913. During operation, one or more or a pluralityof empty magazines 222, potentially having wax thereon, may beintroduced into and closed within the basket.

As shown, the basket may optionally be coupled with a rotation mechanismthat may include a spindle, shaft, or other rotation axis 915 thatrotates to rotate the basket and a motor or other rotation actuator 917to rotate the rotation axis. In the illustration, the basket rotatesalong a horizontal axis, although the basket may alternatively rotatealong a vertical axis. The basket may also optionally move horizontallyor vertically along the horizontal or vertical axis, if desired, forexample to help to improve cleaning, although this is not required.

A bottom portion of the tank may serve as a sump or reservoir. Water 919may be included in the sump or reservoir.

A heater 923 may be disposed in the water and used to increase thetemperature of the water. In one or more embodiments, the temperature ofthe water may be increased to a temperature ranging from about 70° C. toabout 100° C., often from about 75° C. to about 95° C., in some casesfrom about 82° C. to about 87° C. Examples of suitable heaters include,but are not limited to, immersion heaters including an electricresistance heater, boilers of the type used in home hot water heaters,steam coils, and the like. If desired, a heater or temperaturecontroller 925 may optionally be included to control the heater and/orto control the temperature.

A pump 927 or other water movement and/or pressurization device may drawwater from the sump or reservoir through an inlet line 929. The pump maypressurize the water. For example, in one or more embodiments, the pumpmay pressurize the water to a pressure ranging from several hundred PSI(pounds per square inch) to several thousand PSI, and in some cases fromabout 500 PSI to about 1500 PSI. The output of the pump is coupled witha pressurized water line 931 capable of handling the output pressure.

A pressurized water ejection manifold 933 is coupled with thepressurized water line. The manifold may include one or more water jetsor nozzles 935. Three jets or nozzles are shown in the illustratedembodiment, although fewer or more may optionally be included. The jetsor nozzles are generally arranged around the basket so that sprays 937therefrom are directed at substantially all portions of the emptymagazines, at least when the basket is rotated.

The heated water may help to melt wax on the empty magazines. Thepressurized sprays of the water may help to dislodge or remove themelted wax from the empty magazines. The removed wax may fall to thereservoir or sump at the bottom of the tank. There the wax, beinglighter than the water, may tend to float as a melted and immisciblelayer 943 on the water. As shown in one or more embodiments, an openingor inlet to inlet line 929 may be disposed within the water in sump orother bottom portion of the tank well below melted wax layer 943. Thismay help to avoid or at least reduce the drawing of melted wax intoinlet line 929 by the pump.

In one or more embodiments, a ledge, weir, overflow dam, or otherstructure 939 may optionally be included projecting from the bottom ofthe tank upward to an intended level of fluid in the tank. Melted waxmay flow over the ledge, weir, or other structure into a wax removalreservoir 941. Alternatively, the wax may be removed by other means,such as, for example, through a siphon port, from the top of the tank,or otherwise.

A water makeup line 945, such as, for example, connected with a faucetor other water supply, may optionally be used to add additional water tothe tank. If desired, a level control system and a valve on the watermakeup line (not shown) may optionally be included to control the levelof the water in the tank. Collecting the water in the bottom of the tankmay allow the water to be reused.

FIG. 10A is a diagram of another detailed example embodiment of anintegrated tissue processing and embedding system 1010, which forconvenience may simply be referred to as an integrated system. Theintegrated system includes tissue processor 212 and embedding system230. The tissue processor and the embedding system, and their componentsand functions, may optionally be similar to, or the same as, those ofFIG. 2 and/or FIG. 6 and/or FIG. 8.

The integrated system also includes tissue processor/embedding systemintegration unit 1024, or simply the integration unit. The integrationunit has robot 1026. Robot 1026 and its components and functions may besimilar those of robot 226 of FIG. 2 and/or robot 626 of FIG. 6 and/orrobot 826 of FIG. 8, with a few notable exceptions discussed below.

As shown, in one or more embodiments, the robot may have a so-calledCartesian Coordinate type or a gantry type arrangement. The integrationunit includes frame 1083 to provide a structural support for theintegration unit. The frame may be physically coupled or connectedbetween the tissue processor and the embedding system, or justphysically disposed between the tissue processor and the embeddingsystem without physical contact. As shown, frame 1083 may have an openrectangular structure with beams, braces, or other members connectingthe corners. Other frames having other sizes, shapes, and designs arealso suitable.

Other components of the integration unit, such as, for example, astorage location, a heater, a cleaning mechanism, an empty magazinestorage, and a hanger storage location, a controller, which for the sakeof simplicity are not shown, may be housed within and coupled with theframe. For example, commercially available compartments, chambers,tanks, cabinets, or the like, may be introduced into and coupled withthe frame, or, the compartments, cabinets, or the like, may beconstructed onto the frame.

The robot is supported by frame 1083. As viewed, robot 1026 includeshorizontal rail, track, beam, or other member 1084. The horizontalmember is physically coupled or connected with and supported by theframe. The horizontal member is fixedly or statically coupled orconnected in place and for purposes of this discussion its horizontalorientation defines an x-direction.

The horizontal member runs horizontally in a direction of an x-axis,which leads from the tissue processor to the embedding system. Thehorizontal member extends horizontally approximately from above theoutput of the tissue processor to above the input of the embeddingsystem.

The robot also includes vertical rail, track, beam, or other member1085. An uppermost portion of the vertical member is coupled orconnected with the horizontal member at an intersection or “T”. Thevertical track or other member is slideably coupled with the horizontalmember and the vertical member may slide horizontally along thehorizontal member. For purposes of this discussion, the verticalorientation of vertical member 1085 defines a z-direction.

The vertical member runs vertically in a direction of a z-axis, whichleads downward from horizontal member 1084. Vertical member 1085 extendsvertically from horizontal member 1084 down approximately to the lowerof either the output of tissue processor 212 or the input of embeddingsystem 230. In the illustration vertical member 1085 leads downwardtoward the output of tissue processor 212. Vertical member 1085 istypically shorter in length than horizontal member 1084.

The robot also includes carriage 1086. Carriage 1086 is slideably orotherwise moveably mounted on, or otherwise moveably coupled orconnected with, the horizontal and/or vertical members.Representatively, the carriage may be driven or moved by a motorizedmechanism of the type used in Gantry robots. Electrical power may beprovided to the carriage and/or the motor, for example, through a powersupply train or chain along rails defining horizontal member 1084 andvertical member 1085.

Carriage 1086 may move along horizontal member 1084 and vertical member1085. Horizontal member 1084 represents a horizontal linear x-axis ofmovement for the carriage. The vertical member represents a verticallinear z-axis of movement for the carriage. A path of movement ofcarriage 1086 of the robot along horizontal member 1084 is continuouslyconnected with a path of movement of carriage 1086 of the robot alongvertical member 1085. Vertical member 1085 may slide along horizontalmember 1084 and carriage 1086 may slide or travel vertically alongvertical member 1085. Together, the horizontal and vertical membersdefine a continuous path for movement of the carriage from near theoutput of tissue processor 212 to near the input to embedding system230.

One advantage of this vertical member 1085 is that it allows the robotaccess to inputs and outputs having, potentially, different elevations.However, vertical member 1085 is included in the illustrated embodimentto allow the carriage of the robot to reach the output of tissueprocessor 212 and/or the input of embedding system 230. If instead theoutput of tissue processor 212 and the input of embedding system 230were higher, vertical member 1085 may potentially be omitted.

The robot also has arm 1087 and end effector 1088. Arm 1087 is connectedwith carriage 1086. End effector 1088 is connected with an end of arm1087. Many known robot arm designs are suitable.

In one or more embodiments, arm 1087 may have rotation joint or otherrotation mechanism 1089. Rotation mechanism 1089 is connected between anend of arm 1087 of the robot and end effector 1088. The rotation jointor mechanism may allow rotation of the end effector, in some cases in360°. The rotation joint or mechanism combined with the horizontal andvertical members may give the robot at least four-axes of movement. Byway of example, once the carriage is in an appropriate position, therobot may rotate the end effector to achieve a desired orientation toengage with an item, and/or to achieve a desired orientation to placethe item in a location.

Typical Gantry type robots generally have less than four-axes ofmovement. For example, a typical Gantry type robot may have onlythree-axes of movement. Moreover, typical Gantry type robots generallydo not have such a rotation mechanism 1089 that allows end effector 1088to rotate. Still further, a typical Gantry type robot generally does nothave the vertical track or other vertical member, such as verticalmember 1085.

The integration unit also includes controller 1096 electrically,wirelessly, or otherwise linked or in communication with the robot. Asshown, in one or more embodiments, the controller may include a computersystem. Alternatively, the controller may include a programmable logicunit. The controller may include software or other instructions tocontrol the robot. The controller may be programmable and optionallyre-programmable. The controller may signal or communicate with the robotto cause the robot to perform operations as described elsewhere herein.

As shown, in one or more embodiments, controller 1096 may alsooptionally be electrically, wirelessly, or otherwise linked or incommunication with the tissue processor and/or the embedding system. Inone or more embodiments, the controller may receive signals orcommunications from the tissue processor and/or the embedding system,such as, for example indicating status (e.g., a processed magazine isready, the embedding system is ready, an empty magazine is ready in theembedding system, etc.). In one or more embodiments, the controller mayprovide signals or communications to the embedding system and/or thetissue processor to control the embedding system and/or the tissueprocessor to open and/or close their respective inputs and outputs.

In one or more embodiments, the controller may also optionally controlother aspects associated with the operation of the integration unit. Forexample, in one or more embodiments, the controller may control heatingof a storage location (e.g., temperatures, start times, stop times,durations, or some combination thereof). As another example, in one ormore embodiments, the controller may control a cleaning mechanism (e.g.,start times, stop times, temperatures, pressures, or some combinationthereof).

FIG. 10B is an expanded front view of robot 1026 of FIG. 10A. A portionof tissue processor 212 and frame 1083 are shown.

Robot 1026 includes horizontal member 1084 (only a portion of which isshown) coupled with vertical member 1085. The robot also includescarriage 1086. In the illustration, the carriage is coupled with thevertical member. The carriage may slide or otherwise move verticallyalong the vertical member in the direction of vertical arrow 1097. Thecarriage may slide or otherwise move horizontally along the horizontalmember in the direction of horizontal arrow 1098.

The robot also has arm 1087 and end effector 1088. The arm is coupled orconnected with the carriage. The end effector is coupled or connectedwith the end of the arm. As shown, in one or more embodiments, the armmay have rotation joint or other rotation mechanism 1089 to allowrotation of the end effector as shown by rotation arrow 1099. Therotation joint or mechanism combined with the horizontal and verticalmembers may give the robot at least 4-axis of movement. By way ofexample, once the carriage is in an appropriate position, the robot mayrotate the end effector to achieve a desired orientation to engage withan item, and/or to achieve a desired orientation to place the item in alocation.

In one or more embodiments, the end effector may include pincers, claws,jaws, hook-like structures or another gripper. As shown in theillustration, in one aspect, the gripper may grip handle 447 having twomagazines 222A/B attached.

FIG. 10C is an expanded side partial perspective view of an embodimentof end effector 1088. The end effector is holding handle 1047 havingmagazines 222 attached. A portion of vertical member 1085 is also shown.

The end effector has end effector body 1047 and fixed jaw or other fixedmember 1049. The fixed jaw has hook-like structure 1051. The hook-likestructure may be introduced through an opening 1053 in handle 1047.Upper portion 1055 of the handle may rest on the hook-like structure.The handle may hang from the hook-like structure. In one or moreembodiments, either the handle or the hook-like structure may include analignment feature, such as, for example, a notch, groove, depression, orthe like, to provide centering or other desired positioning of thehandle on the hook-like structure.

The end effector also has movable jaw or other movable member 1057. Themovable member may optionally move horizontally toward the hook-likestructure in the direction of arrow 1059. The horizontal movement maycontinue until a lowermost portion 1061 of the movable jaw contacts thehandle. This may help to stabilize the handle and/or reduce swaying orswinging during movement.

In one or more embodiments, the movable jaw may be used to remove thehandle from the magazines. Initially, the handle having the magazinesattached may hang from the hook-like structure as shown in FIG. 10C. Inone particular embodiment, the magazines may be set down or placed intoa conforming cavity or chamber, such as, for example, a rectangularshaped chamber having a floor and vertical sidewalls that is sizedslightly larger than the two magazines. While the handle is pinched orheld between fixed member 1049 and movable member 1057, the end effectormay move away from the magazines in the reverse direction of arrow 1059(to the left in the illustration). Since the magazines are in theconforming cavity, they may remain stationary while the handle is pulledin the reverse direction of arrow 1059. The handle may slide away fromthe magazines along grooves at the top of the magazines until it hasbeen freed from the magazines.

In one or more embodiments, the movable jaw may be used to clamp amagazine after the handle has been removed. Lower portion 1065 of thefixed jaw may have a small flat surface where a magazine may restagainst. The robot may move until the magazine is against or very nearthe small flat surface of the lower portion of the fixed jaw. Themovable jaw may then move horizontally toward the magazine, in thedirection of arrow 1059, until lowermost portion 1061 of the movable jawcontacts the magazine and applies a compression force on the magazinesagainst the small flat surface of the lower portion of the fixed jaw.That is, the movable and fixed jaws may hold the magazine much like aC-clamp or G-clamp would. In one or more embodiments, lowermost portion1061 of movable jaw 1057 may engage a magazine at the aforementionedgrooves at the top of the magazine. (Recall that the handle slides awayfrom the magazines along grooves at the top of the magazines.)Utilization of such grooves may help to improve gripping or engaging themagazine, but is not required.

This is just one example of a suitable integration unit and robot.Various other integration units and robots are contemplated, and will beapparent to those skilled in the art, and having the benefit of thepresent disclosure. As one example, another suitable robot is anarticulated robot situated in front of, behind, or between the tissueprocessor and the embedding system, and having a sufficiently long andflexible arm to provide a work envelope encompassing the output of thetissue processor and the input of the embedding system. As anotherexample, yet another suitable robot is an articulated robot situated ator on either the tissue processor or the embedding system, and having asufficiently long and flexible arm to provide a work envelopeencompassing the output of the tissue processor and the input of theembedding system. As yet another example, a still further suitable robotis an articulated robot coupled in a Gantry or Cartesian coordinate typerobot configuration. Still other suitable robots are contemplated.

It is not required that an integration unit and/or a robot transfermagazines or other tissue holders all the way between a tissue processorand an embedding system. Some of the advantage may be achieved if theintegration unit and/or the robot transfers the magazines part waybetween the tissue processor and the embedding system with another partof the transfer being performed manually.

FIG. 11 is a block diagram of a fifth embodiment of integrated tissueprocessing and embedding system 1110, which may be referred to simply asthe integrated system, along with an embedding system 230. Theintegrated system includes tissue processor 212, and tissueprocessor/embedding system integration unit 1124, which for may bereferred to simply as the integration unit. The tissue processor hasoutput 220. The integration unit has storage location 1124 and robot1126.

In one or more embodiments, integration unit 1124 and robot 1126 may befunctionally or operatively coupled or connected with tissue processor212, but not with embedding system 230. In one or more embodiments, asshown by arrow 1157, the robot may transfer magazine 222A from output220 of the tissue processor to storage location 1156 of the integrationunit as magazine 222B. Magazine 222B may be transferred from the storagelocation to the embedding system manually.

FIG. 12 is a block diagram of a sixth embodiment of integrated tissueprocessing and embedding system 1210, which may simply be referred to asthe integrated system, along with a tissue processor 212. The integratedsystem includes embedding system 230, and tissue processor/embeddingsystem integration unit 1224, which may simply be referred to as theintegration unit. The integration unit has storage location 1256 androbot 1226. The embedding system has input 238.

In one or more embodiments, integration unit 1224 and robot 1226 may befunctionally or operatively coupled or connected with embedding system230, but not with tissue processor 212. In one or more embodiments, asshown by arrow 1259, the robot may transfer magazine 222A from storagelocation 1256 of the integration unit to input 238 of the embeddingsystem as magazine 222B. Previously, magazine 222A may have beenmanually transferred from an output of the tissue processor to thestorage location.

Aside from these differences, the tissue processors, embedding systems,and integration units, of FIGS. 11 and 12, and their components andfunctions, may optionally be similar to, or the same as, those of FIG.2, and/or FIG. 6, and/or FIG. 8.

In one or more embodiments, an integration units described herein mayoptionally have a switch, button, or other mechanism to disable theintegration unit, the robot, or both. This may allow operations to beperformed manually, instead of by the robot. Switches, buttons, or othermechanisms may optionally be included, or retained, on the tissueprocessor and the embedding system to allow the output and input,respectively, to be opened and closed manually.

One or more embodiments pertain to a method of retrofitting or modifyingan existing tissue processor and/or an existing embedding system toincorporate a tissue processor/embedding system integration unit and/ora robot as disclosed elsewhere herein. The method may includefunctionally or operatively coupling or connecting the integration unitand/or the robot with the tissue processor and/or the embedding system.

In one or more embodiments, the tissue processor and/or the embeddingsystem may optionally be minimally modified so that an output of thetissue processor and/or an input of the embedding system mayautonomously open and close.

One or more embodiments pertain to a kit having a tissueprocessor/embedding system integration unit and/or a robot, as describedelsewhere herein, which may be used to retrofit or modify an existingtissue processor and/or an existing embedding system.

The kit may also include instructions, such as, for example installationor assembly instructions and/or use (e.g., programming) instructions.

FIG. 13 is a diagram of a seventh embodiment of an even more highlyintegrated tissue processing and embedding system 1310, which forconvenience may simply be referred to as the integrated system. Theintegrated system includes input 1321, tissue processing mechanism 1314,embedding mechanism 1332, output 1339, and robot 1326. The input and thetissue processing mechanism may be similar to those found inconventional tissue processors. Likewise, the embedding mechanism andoutput may be similar to those found in conventional embedding systems.

The input may receive potentially grossed and fixated tissue within oneor more tissue holders. The robot is functionally or operatively coupledto move or transfer the tissue within one or more tissue holders fromthe input to the tissue processing mechanism, from the tissue processingmechanism to the embedding mechanism, and from the embedding mechanismto the output. The embedded tissues may be removed from the output.

Integrated system 1310 has an even higher level of integration that theintegrated systems shown in FIGS. 2, 6, 8, and 10. The input, the tissueprocessing mechanism, the embedding mechanism, the output, and therobot, may all be included within a housing or enclosure of a singlesystem or instrument, instead of being separated instruments that havebeen integrated together for example by an intervening integration unit.

In the description and claims, the terms “coupled” and “connected,”along with their derivatives, may be used. It should be understood thatthese terms are not intended as synonyms for each other. Rather, inparticular embodiments, “connected” may be used to indicate that two ormore elements are in direct physical or electrical contact with eachother. “Coupled” may mean that two or more elements are in directphysical or electrical contact. However, “coupled” may also mean thattwo or more elements are not in direct contact with each other, but yetstill co-operate or interact with each other.

In the description above, for the purposes of explanation, numerousspecific details have been set forth in order to provide a thoroughunderstanding of the embodiments. It will be apparent however, to oneskilled in the art, that one or more other embodiments may be practicedwithout some of these specific details. The particular embodimentsdescribed are not provided to limit the invention but to illustrateembodiments thereof. The scope of the invention is not to be determinedby the specific examples provided above, but only by the claims below.In other instances, well-known components, mechanisms, structures,devices, and operations have been shown in block diagram form or withoutdetail in order to avoid obscuring the understanding of the description.

It will also be appreciated, by one skilled in the art, thatmodifications may be made to the embodiments disclosed herein, such as,for example, to the sizes, configurations, forms, functions, and mannerof operation, and use, of the components of the embodiments. Allequivalent relationships to those illustrated in the drawings anddescribed in the specification are encompassed within embodiments of theinvention. Where considered appropriate, reference numerals or terminalportions of reference numerals have been repeated among the figures toindicate corresponding or analogous elements, which unless specifiedotherwise may optionally have similar characteristics.

Various operations and methods have been described. Some of the methodshave been described in a basic form, but operations may optionally beadded to and/or removed from the methods. The operations of the methodsmay also often optionally be performed in different order.

One or more embodiments of the invention may be provided as a programproduct or other article of manufacture that may include amachine-readable medium having stored thereon one or more instructions.The medium may provide instructions, which, if executed by a machinesuch as a robot or integration unit, may result in and/or cause themachine to perform one or more of the operations or methods disclosedherein. Suitable machines include, but are not limited to, robots,integration units, computer systems, laboratory equipment, and a widevariety of other machines, to name just a few examples.Representatively, the medium may include recordable mediums, such as,for example, floppy diskette, optical storage medium, optical disk,CD-ROM, magnetic disk, magneto-optical disk, read only memory (ROM),programmable ROM (PROM), erasable-and-programmable ROM (EPROM),electrically-erasable-and-programmable ROM (EEPROM), random accessmemory (RAM), static-RAM (SRAM), dynamic-RAM (DRAM), Flash memory, othertypes of memory, other machine-readable medium within programmable logicunits used to control robots, and combinations thereof.

It should also be appreciated that reference throughout thisspecification to “one embodiment”, “an embodiment”, or “one or moreembodiments”, for example, means that a particular feature may beincluded in the practice of the invention. Similarly, it should beappreciated that in the description various features are sometimesgrouped together in a single embodiment, Figure, or description thereoffor the purpose of streamlining the disclosure and aiding in theunderstanding of various inventive aspects. This method of disclosure,however, is not to be interpreted as reflecting an intention that theinvention requires more features than are expressly recited in eachclaim. Rather, as the following claims reflect, inventive aspects maylie in less than all features of a single disclosed embodiment. Thus,the claims following the Detailed Description are hereby expresslyincorporated into this Detailed Description, with each claim standing onits own as a separate embodiment of the invention.

What is claimed is:
 1. A tissue processor/embedding system integrationunit, the tissue processor/embedding system integration unit comprising:a robot having an arm and an end effector coupled with the arm, whereinthe robot is disposed between a tissue processor and an embeddingsystem, wherein the robot has a work envelope, wherein the work envelopeof the robot encompasses an output of the tissue processor, wherein thetissue processor is operable to remove water from tissue and infiltratean embedding agent into the tissue, wherein the work envelope of therobot encompasses an input of the embedding system, wherein theembedding system is operable to embed the tissue from which the waterhas been removed and into which the embedding agent has been infiltratedin a block of an embedding medium, wherein the robot has movement in atleast 4-axis; and instructions stored on a machine-readable medium toconfigure the robot to transfer a tissue holder having the tissue, fromwhich the water has been removed and into which the embedding agent hasbeen infiltrated, from the output of the tissue processor to the inputof the embedding system.
 2. An apparatus comprising: a robot comprisinga work envelope that encompasses a first location having a tissue holderand a different second location comprising an input of an embeddingsystem, wherein the tissue holder is operable to contain at least oneprocessed tissue from which water has been removed and an embeddingagent has been infiltrated, wherein the robot is operable to transferthe tissue holder from the first location to the second location, andwherein the embedding system is operable to embed a processed tissue ina block of an embedding medium.
 3. The apparatus of claim 2, furthercomprising instructions stored on a machine-readable medium to configurethe robot to transfer the tissue holder from the location to the inputof the embedding system.
 4. The apparatus of claim 2, in which the robotis physically disposed between the embedding system and a tissueprocessor.
 5. The apparatus of claim 2, in which the first locationcomprises an output of a tissue processor.
 6. The apparatus of claim 2,further comprising a storage location serving as the location, in whichthe storage location is located outside of the embedding system andoutside of a tissue processor.
 7. The apparatus of claim 6, furthercomprising a heater to heat the storage location.
 8. The apparatus ofclaim 7, in which the embedding agent comprise wax, and in which theheater is operable to heat the wax to a softening or melting point overa period ranging from 2 to 20 minutes.
 9. The apparatus of claim 7, inwhich the heater comprises at least one of a heat lamp, a heating coil,a heating element, a resistance heater, a hot plate, a hot pad, one ormore pipes having hot water or other heating fluid flowing through them,an electric heater, a radiative heater, a space heater, and acombination thereof.
 10. The apparatus of claim 6, in which the robot isconfigured to transfer the tissue holder from an output of a tissueprocessor to the storage location before transferring the tissue holderto the input of the embedding system.
 11. The apparatus of claim 2, inwhich the work envelope encompasses an empty tissue holder output of theembedding system, and in which the robot is configured to move an emptytissue holder away from the empty tissue holder output.
 12. Theapparatus of claim 11, further comprising a cleaning mechanism to cleanthe empty tissue holder, in which the robot is configured to move theempty tissue holder to the cleaning mechanism.
 13. The apparatus ofclaim 12, in which the cleaning mechanism is operable to remove wax fromthe empty tissue holder, and in which the cleaning mechanism comprisesat least one of a spray of heated and pressurized water, a bath of adewaxing composition, a shower of a dewaxing composition, a heated waterbath, a heated water shower, a steam treatment, a scrubbing mechanism,and a combination thereof.
 14. The apparatus of claim 12, wherein thecleaning mechanism comprises a spray of heated and pressurized water, inwhich the heated water has a temperature ranging from 70° C. to 100° C.,and in which the water used to form the spray has a pressure rangingfrom several hundred to several thousand pounds per square inch (PSI).15. The apparatus of claim 2, in which the robot has at least 4-axis.16. The apparatus of claim 2, in which the robot comprises: a horizontalmember leading from the embedding system to a tissue processor; acarriage moveably coupled with the horizontal member; and an arm havingan end effector coupled with the carriage.
 17. The apparatus of claim16, further comprising a vertical member coupled with and leadingdownward from the horizontal member, in which the carriage is alsomoveably coupled with the vertical member, and in which the armcomprises a rotation mechanism.
 18. An integrated tissue processor andembedding system, the integrated tissue processor and embedding systemcomprising: an input to allow a tissue holder operable to contain atissue to be input; a tissue processing mechanism, wherein the tissueprocessing mechanism is operable to process tissue to remove water froma tissue and infiltrate an embedding agent into the tissue; an embeddingmechanism, wherein the embedding mechanism is operable to embedprocessed tissue in a block of an embedding medium; an output to allowthe block embedded tissue to be output; a robot; and instructions storedon a machine-readable medium to configure the robot to transferprocessed tissue from the tissue processing mechanism to the embeddingmechanism.